Although women with HFrEF (heart failure with reduced ejection fraction) present with fewer comorbidities and have a higher survival rate, they experience a poorer quality of life and receive suboptimal treatment when compared with men with the same condition, according to a study published in the Journal of the American College of Cardiology.1
Researchers reviewed randomized controlled trials involving pharmacological therapy from the PARADIGM-HF (ClinicalTrials.gov identifier: NCT01035255)2 and ATMOSPHERE (ClinicalTrials.gov identifier: NCT00853658)3 trials to identify the treatment and outcome differences between women and men. After patients met inclusion criteria for their respective trial, angiotensin-converting enzyme inhibitors or angiotensin receptor blocker therapy were stopped and participants began a regimen of enalapril followed by sacubitril/valsartan in the PARADIGM-HF trial and enalapril followed by the combination of enalapril plus aliskiren in the ATMOSPHERE trial.
The mean follow-up time frames were 26.6 months for the PARADIGM-HF trial and 36.7 months for the ATMOSPHERE trial. Outcomes for both trials were heart failure hospitalizations and cardiovascular deaths. For this study, researchers also analyzed all causes of death, all causes of hospitalizations, and health-related quality of life.
Of the 15,415 participant data analyzed, 21.8% were women from 55 different countries. On average, women were 2 years older (P <.0001), had a higher systolic blood pressure (P <.0001), had an increased heart rate (P <.0001), and were more likely to be obese (33.4% vs 29.2%, P <.001) when compared with men. While women did experience an increase in likelihood of hypertension (70.6% vs 65.5%, P <.0001) and clinically significant valve disease (5.3% vs 4.6%, P =.084), all other comorbidities were lower when compared with men. Women were less likely to be a current smoker (6.2% vs 15.8%, P <.001), had lower alcohol consumption (P <.001), and were more likely to have moderate to extreme anxiety or depression (44.0% vs 29.0%, P <.0001, PARADIGM-HF trial only).
At baseline, women had fewer prior hospitalizations for heart failure (58.1% vs 62.3%, P <.0001), were less likely to have ischemic etiology (50.0% vs 60.5%, P <.001) and were more likely to have dyspnea on effort (88.7% vs 84.7%, P <.0001), a higher left ventricular ejection fraction (29.6% vs 28.8%, P <.0001), a higher New York Heart Association functional class (P <.001), and a lower Kansas City Cardiomyopathy Questionnaire score (P =.001).
For treatment, women were less likely to receive statins (47.6% vs 56.3%), aspirin (46.4% vs 53.0%), anticoagulants (26.7% vs 32.4%), and devices than men (P <.0001 for all).
Women experienced a lower rate of hospitalization due to heart failure (adjusted hazard ratio [HR]= 0.80; 95% CI, 0.72-0.89; P <.001), a lower risk of cardiovascular death (HR=0.70; 95% CI, 0.63-0.77; P <.001), and a lower risk of a myocardial infarction (HR=0.79; 95% CI, 0.63-1.00; P =.048) but had a higher risk of stroke (HR=1.22; 95% CI, 0.99-1.50; P =.062) than men.
The study researchers determined that “[w]omen continue to receive suboptimal treatment, compared with men, with no obvious explanation for this shortfall.” Furthermore, “although women with [HFrEF] live longer than men do, their additional years of life are of poorer quality, with greater self-reported psychological and physical disability,” concluded the researchers.
Future studies need to further examine potential causes behind the sex-related differences in treatments and outcomes as well as focus on treatment options, including tailored therapeutic plans, referrals to cardiac rehabilitation programs, and psychosocial support for women with HFrEF.
Disclosures: The ATMOSPHERE and PARADIGM-HF trials were funded by Novartis. Multiple authors disclosed affiliations with pharmaceutical companies. See the reference for complete disclosure information.
- Dewan P, Rørth R, Jhund PS et al. Differential impact of heart failure with reduced ejection fraction on men and women. J Am Coll Cardiol. 2019;73(1):29-40.
- McMurray JJV, Packer M, Desai AS, et al; PARADIGM-HF Investigators and Committees. Angiotensin–neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004.
- McMurray JJV, Krum H, Abraham WT, et al; ATMOSPHERE Committees Investigators. Aliskiren, enalapril, or aliskiren and enalapril in heart failure. N Engl J Med. 2016;374(16):1521-1532.